Macias-Kauffer, LR; Acuna-Alonzo, V; Del-Rio-Navarro, BE; Bortolini, MC; Gallo, C; Bedoya, G; Rothhammer, F; Gonzalez-Jose, R; Ruiz-Linares, A; Stephens, CR; Velazquez-Cruz, R; Villamil-Ramirez, H; Fernandez del Valle-Laisequilla, C; Reyes-Garcia, JG; Barranco Gardno, LM; Carrasco-Portugal, M; Flores-Murrieta, FJ; Vargas-Alarcon, G; Canizales-Quinteros, S; Villarreal-Molina, T; Canizales-Quinteros, S; Leon-Mimila, P; Jacobo-Albavera, L; Posadas-Romero, C; Posadas-Sanchez, R; Lopez-Contreras, BE; Moran-Ramos, S; Romero-Hidalgo, S; ,
Background: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there arc few GWAS in Latino populations, and the role of SUA-associatal single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population.Methods: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD.Results: Only two loci were associated with SUA levels: SLC2A9( beta = -0.47 mg/dl, P = 1.57 x 10(-42) for lead SNP rs7678287) and ABCG2 023 mg /dl, P 2.42 x 10-1 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGER), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group.Conclusions: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABC'62) did not support a causal role of elevated SUA levels for premature CAD. (C) 2018 Elsevier B.V. All rights reserved.